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Protein

C-C motif chemokine 8

Gene

CCL8

Organism
Homo sapiens (Human)
Status
Reviewed-Annotation score: Annotation score: 5 out of 5-Experimental evidence at protein leveli

Functioni

Chemotactic factor that attracts monocytes, lymphocytes, basophils and eosinophils. May play a role in neoplasia and inflammatory host responses. This protein can bind heparin. The processed form MCP-2(6-76) does not show monocyte chemotactic activity, but inhibits the chemotactic effect most predominantly of CCL7, and also of CCL2 and CCL5 and CCL8.1 Publication

GO - Molecular functioni

  1. chemokine activity Source: ProtInc
  2. heparin binding Source: UniProtKB-KW
  3. phospholipase activator activity Source: UniProtKB
  4. protein kinase activity Source: UniProtKB

GO - Biological processi

  1. calcium ion transport Source: UniProtKB
  2. cell-cell signaling Source: UniProtKB
  3. cell chemotaxis Source: GOC
  4. cellular calcium ion homeostasis Source: UniProtKB
  5. chemotaxis Source: ProtInc
  6. exocytosis Source: UniProtKB
  7. immune response Source: InterPro
  8. inflammatory response Source: UniProtKB-KW
  9. positive regulation of catalytic activity Source: GOC
  10. protein phosphorylation Source: GOC
  11. response to virus Source: ProtInc
  12. signal transduction Source: ProtInc
Complete GO annotation...

Keywords - Molecular functioni

Cytokine

Keywords - Biological processi

Chemotaxis, Inflammatory response

Keywords - Ligandi

Heparin-binding

Names & Taxonomyi

Protein namesi
Recommended name:
C-C motif chemokine 8
Alternative name(s):
HC14
Monocyte chemoattractant protein 2
Monocyte chemotactic protein 2
Short name:
MCP-2
Small-inducible cytokine A8
Cleaved into the following chain:
Gene namesi
Name:CCL8
Synonyms:MCP2, SCYA10, SCYA8
OrganismiHomo sapiens (Human)
Taxonomic identifieri9606 [NCBI]
Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo
ProteomesiUP000005640 Componenti: Chromosome 17

Organism-specific databases

HGNCiHGNC:10635. CCL8.

Subcellular locationi

GO - Cellular componenti

  1. extracellular space Source: UniProtKB-KW
Complete GO annotation...

Keywords - Cellular componenti

Secreted

Pathology & Biotechi

Organism-specific databases

PharmGKBiPA35567.

PTM / Processingi

Molecule processing

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Signal peptidei1 – 2323CuratedAdd
BLAST
Chaini24 – 9976C-C motif chemokine 8PRO_0000005188Add
BLAST
Chaini29 – 9971MCP-2(6-76)PRO_0000005189Add
BLAST

Amino acid modifications

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Modified residuei24 – 241Pyrrolidone carboxylic acid1 Publication
Disulfide bondi34 ↔ 591 Publication
Disulfide bondi35 ↔ 751 Publication

Post-translational modificationi

N-terminal processed form MCP-2(6-76) is produced by proteolytic cleavage after secretion from peripheral blood monocytes.1 Publication

Keywords - PTMi

Disulfide bond, Pyrrolidone carboxylic acid

Proteomic databases

PaxDbiP80075.
PRIDEiP80075.

Miscellaneous databases

PMAP-CutDBP80075.

Expressioni

Tissue specificityi

Highest expression found in the small intestine and peripheral blood cells. Intermediate levels seen in the heart, placenta, lung, skeletal muscle, thymus, colon, ovary, spinal cord and pancreas. Low levels seen in the brain, liver, spleen and prostate.

Inductioni

By IFNG/IFN-gamma, mitogens and IL1/interleukin-1.

Gene expression databases

BgeeiP80075.
CleanExiHS_CCL8.
ExpressionAtlasiP80075. baseline and differential.
GenevestigatoriP80075.

Interactioni

Subunit structurei

Monomer or homodimer; in equilibrium.1 Publication

Protein-protein interaction databases

BioGridi112258. 2 interactions.
DIPiDIP-5871N.
MINTiMINT-103111.
STRINGi9606.ENSP00000225840.

Structurei

Secondary structure

1
99
Legend: HelixTurnBeta strand
Show more details
Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Turni26 – 294Combined sources
Helixi45 – 473Combined sources
Beta strandi48 – 536Combined sources
Beta strandi59 – 613Combined sources
Beta strandi64 – 685Combined sources
Beta strandi73 – 764Combined sources
Helixi81 – 9616Combined sources

3D structure databases

Select the link destinations:
PDBei
RCSB PDBi
PDBji
Links Updated
EntryMethodResolution (Å)ChainPositionsPDBsum
1ESRX-ray2.00A24-99[»]
ProteinModelPortaliP80075.
SMRiP80075. Positions 24-99.
ModBaseiSearch...
MobiDBiSearch...

Miscellaneous databases

EvolutionaryTraceiP80075.

Family & Domainsi

Sequence similaritiesi

Keywords - Domaini

Signal

Phylogenomic databases

eggNOGiNOG75507.
GeneTreeiENSGT00730000110714.
HOGENOMiHOG000036686.
HOVERGENiHBG017871.
InParanoidiP80075.
KOiK16596.
OMAiSMKHLDQ.
OrthoDBiEOG7C5MC2.
PhylomeDBiP80075.
TreeFamiTF334888.

Family and domain databases

InterProiIPR000827. Chemokine_CC_CS.
IPR001811. Chemokine_IL8-like_dom.
[Graphical view]
PfamiPF00048. IL8. 1 hit.
[Graphical view]
SMARTiSM00199. SCY. 1 hit.
[Graphical view]
SUPFAMiSSF54117. SSF54117. 1 hit.
PROSITEiPS00472. SMALL_CYTOKINES_CC. 1 hit.
[Graphical view]

Sequencei

Sequence statusi: Complete.

Sequence processingi: The displayed sequence is further processed into a mature form.

P80075-1 [UniParc]FASTAAdd to basket

« Hide

        10         20         30         40         50
MKVSAALLCL LLMAATFSPQ GLAQPDSVSI PITCCFNVIN RKIPIQRLES
60 70 80 90
YTRITNIQCP KEAVIFKTKR GKEVCADPKE RWVRDSMKHL DQIFQNLKP
Length:99
Mass (Da):11,246
Last modified:November 1, 1997 - v2
Checksum:i9D67976BB9422F2A
GO

Sequence cautioni

The sequence CAA68168.1 differs from that shown. Reason: Erroneous initiation. Curated

Natural variant

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Natural varianti14 – 141A → V.
Corresponds to variant rs35401229 [ dbSNP | Ensembl ].
VAR_048704
Natural varianti69 – 691K → Q.3 Publications
Corresponds to variant rs1133763 [ dbSNP | Ensembl ].
VAR_001633

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
X99886 Genomic DNA. Translation: CAA68168.1. Different initiation.
Y10802 mRNA. Translation: CAA71760.1.
Y16645 mRNA. Translation: CAA76341.1.
BC126242 mRNA. Translation: AAI26243.1.
CCDSiCCDS11280.1.
PIRiJC5295.
RefSeqiNP_005614.2. NM_005623.2.
UniGeneiHs.271387.

Genome annotation databases

EnsembliENST00000394620; ENSP00000378118; ENSG00000108700.
GeneIDi6355.
KEGGihsa:6355.
UCSCiuc002hib.3. human.

Polymorphism databases

DMDMi2506280.

Keywords - Coding sequence diversityi

Polymorphism

Cross-referencesi

Web resourcesi

Wikipedia

CCL8 entry

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
X99886 Genomic DNA. Translation: CAA68168.1. Different initiation.
Y10802 mRNA. Translation: CAA71760.1.
Y16645 mRNA. Translation: CAA76341.1.
BC126242 mRNA. Translation: AAI26243.1.
CCDSiCCDS11280.1.
PIRiJC5295.
RefSeqiNP_005614.2. NM_005623.2.
UniGeneiHs.271387.

3D structure databases

Select the link destinations:
PDBei
RCSB PDBi
PDBji
Links Updated
EntryMethodResolution (Å)ChainPositionsPDBsum
1ESRX-ray2.00A24-99[»]
ProteinModelPortaliP80075.
SMRiP80075. Positions 24-99.
ModBaseiSearch...
MobiDBiSearch...

Protein-protein interaction databases

BioGridi112258. 2 interactions.
DIPiDIP-5871N.
MINTiMINT-103111.
STRINGi9606.ENSP00000225840.

Polymorphism databases

DMDMi2506280.

Proteomic databases

PaxDbiP80075.
PRIDEiP80075.

Protocols and materials databases

DNASUi6355.
Structural Biology KnowledgebaseSearch...

Genome annotation databases

EnsembliENST00000394620; ENSP00000378118; ENSG00000108700.
GeneIDi6355.
KEGGihsa:6355.
UCSCiuc002hib.3. human.

Organism-specific databases

CTDi6355.
GeneCardsiGC17P032646.
HGNCiHGNC:10635. CCL8.
MIMi602283. gene.
neXtProtiNX_P80075.
PharmGKBiPA35567.
GenAtlasiSearch...

Phylogenomic databases

eggNOGiNOG75507.
GeneTreeiENSGT00730000110714.
HOGENOMiHOG000036686.
HOVERGENiHBG017871.
InParanoidiP80075.
KOiK16596.
OMAiSMKHLDQ.
OrthoDBiEOG7C5MC2.
PhylomeDBiP80075.
TreeFamiTF334888.

Miscellaneous databases

ChiTaRSiCCL8. human.
EvolutionaryTraceiP80075.
GeneWikiiCCL8.
GenomeRNAii6355.
NextBioi24684.
PMAP-CutDBP80075.
PROiP80075.
SOURCEiSearch...

Gene expression databases

BgeeiP80075.
CleanExiHS_CCL8.
ExpressionAtlasiP80075. baseline and differential.
GenevestigatoriP80075.

Family and domain databases

InterProiIPR000827. Chemokine_CC_CS.
IPR001811. Chemokine_IL8-like_dom.
[Graphical view]
PfamiPF00048. IL8. 1 hit.
[Graphical view]
SMARTiSM00199. SCY. 1 hit.
[Graphical view]
SUPFAMiSSF54117. SSF54117. 1 hit.
PROSITEiPS00472. SMALL_CYTOKINES_CC. 1 hit.
[Graphical view]
ProtoNetiSearch...

Publicationsi

« Hide 'large scale' publications
  1. "The human MCP-2 gene (SCYA8): cloning, sequence analysis, tissue expression, and assignment to the CC chemokine gene contig on chromosome 17q11.2."
    van Coillie E., Fiten P., Nomiyama H., Sakaki Y., Miura R., Yoshie O., van Damme J., Opdenakker G.
    Genomics 40:323-331(1996) [PubMed] [Europe PMC] [Abstract]
    Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA], VARIANT GLN-69.
  2. "Human monocyte chemotactic protein-2: cDNA cloning and regulated expression of mRNA in mesenchymal cells."
    van Coillie E., Froyen F., Nomiyama H., Miura R., Fiten P., van Aelst I., van Damme J., Opdenakker G.
    Biochem. Biophys. Res. Commun. 231:726-730(1996) [PubMed] [Europe PMC] [Abstract]
    Cited for: NUCLEOTIDE SEQUENCE [MRNA], VARIANT GLN-69.
    Tissue: Bone marrow.
  3. "The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC)."
    The MGC Project Team
    Genome Res. 14:2121-2127(2003) [PubMed] [Europe PMC] [Abstract]
    Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA], VARIANT GLN-69.
  4. "Cloning and expression of a gamma-interferon-inducible gene in monocytes: a new member of a cytokine gene family."
    Chang H.C., Hsu F., Freeman G.J., Griffin J.D., Reinherz E.L.
    Int. Immunol. 1:388-397(1988) [PubMed] [Europe PMC] [Abstract]
    Cited for: NUCLEOTIDE SEQUENCE [MRNA] OF 23-99.
  5. "Structural and functional identification of two human, tumor-derived monocyte chemotactic proteins (MCP-2 and MCP-3) belonging to the chemokine family."
    van Damme J., Proost P., Lenaerts J.-P., Opdenakker G.
    J. Exp. Med. 176:59-65(1991) [PubMed] [Europe PMC] [Abstract]
    Cited for: PROTEIN SEQUENCE OF 26-99.
    Tissue: Osteosarcoma.
  6. "Structural characterization of a monomeric chemokine: monocyte chemoattractant protein-3."
    Kim K.-S., Rajarathnam K., Clark-Lewis I., Sykes B.D.
    FEBS Lett. 395:277-282(1995) [PubMed] [Europe PMC] [Abstract]
    Cited for: SUBUNIT.
  7. "Posttranslational modifications affect the activity of the human monocyte chemotactic proteins MCP-1 and MCP-2: identification of MCP-2(6-76) as a natural chemokine inhibitor."
    Proost P., Struyf S., Couvreur M., Lenaerts J.-P., Conings R., Menten P., Verhaert P., Wuyts A., Van Damme J.
    J. Immunol. 160:4034-4041(1997) [PubMed] [Europe PMC] [Abstract]
    Cited for: IDENTIFICATION OF MCP-2(6-76), IDENTIFICATION BY MASS SPECTROMETRY, PROTEOLYTIC PROCESSING OF N-TERMINAL, FUNCTION.
  8. "Complete crystal structure of monocyte chemotactic protein-2, a CC chemokine that interacts with multiple receptors."
    Blaszczyk J., Coillie E.V., Proost P., Damme J.V., Opdenakker G., Bujacz G.D., Wang J.M., Ji X.
    Biochemistry 39:14075-14081(1999) [PubMed] [Europe PMC] [Abstract]
    Cited for: X-RAY CRYSTALLOGRAPHY (2.0 ANGSTROMS) OF 24-99, PYROGLUTAMATE FORMATION AT GLN-24, DISULFIDE BONDS.

Entry informationi

Entry nameiCCL8_HUMAN
AccessioniPrimary (citable) accession number: P80075
Secondary accession number(s): A0AV77, P78388
Entry historyi
Integrated into UniProtKB/Swiss-Prot: December 1, 1992
Last sequence update: November 1, 1997
Last modified: January 7, 2015
This is version 148 of the entry and version 2 of the sequence. [Complete history]
Entry statusiReviewed (UniProtKB/Swiss-Prot)
Annotation programChordata Protein Annotation Program
DisclaimerAny medical or genetic information present in this entry is provided for research, educational and informational purposes only. It is not in any way intended to be used as a substitute for professional medical advice, diagnosis, treatment or care.

Miscellaneousi

Keywords - Technical termi

3D-structure, Complete proteome, Direct protein sequencing, Reference proteome

Documents

  1. Human chromosome 17
    Human chromosome 17: entries, gene names and cross-references to MIM
  2. Human entries with polymorphisms or disease mutations
    List of human entries with polymorphisms or disease mutations
  3. Human polymorphisms and disease mutations
    Index of human polymorphisms and disease mutations
  4. MIM cross-references
    Online Mendelian Inheritance in Man (MIM) cross-references in UniProtKB/Swiss-Prot
  5. PDB cross-references
    Index of Protein Data Bank (PDB) cross-references
  6. SIMILARITY comments
    Index of protein domains and families

External Data

Dasty 3

Similar proteinsi

Links to similar proteins from the UniProt Reference Clusters (UniRef) at 100%, 90% and 50% sequence identity:
100%UniRef100 combines identical sequences and sub-fragments with 11 or more residues from any organism into Uniref entry.
90%UniRef90 is built by clustering UniRef100 sequences that have at least 90% sequence identity to, and 80% overlap with, the longest sequence (a.k.a seed sequence).
50%UniRef50 is built by clustering UniRef90 seed sequences that have at least 50% sequence identity to, and 80% overlap with, the longest sequence in the cluster.